An elevated level of homocyst(e)ine (H(e)) is an independent risk factor for atherosclerosis and its sequelae. It is known that folic acid decreases plasma H(e) concentration in normal individuals. Therefore, an unmasked, multicenter, randomized Phase II clinical trial was conducted to determine the dose response to folic acid in reducing H(e) levels in acute stroke patients. Forty-eight patients were randomized from five sites; complete data from 37 patients were analyzed. Three dose levels for daily folic acid intake were used 12.5 fg (low dose), 2.5 mg (medium dose), and 5 mg (high dose). Folic acid intake was continued for 60 days, with follow-up visits for drug adherence and blood collection at 30 and 60 days. H(e) and B12, B6, and folate levels were recorded. The mean H(e) was 15.4 nmol/mL at baseline. Low, medium, and high dose treatments were associated with an average decrease in H(e) of 1.96, 2.91 and 3.68 nmol/mL, respectively. The change in the high dose group is statistically significant using the two-sided sign test (p = 0.01); change in the medium dose group is marginally significant (p=0.06). The one-sided JonckeereTerpstra test of a dose-response effect is marginally significant (0.07). We conclude that this data provides evidence that folic acid, at daily doses of 2.5 and 5 mg, decreases H(e) in acute stroke patients. In addition, these data suggest a possible dose-response effect.